We have proposed that the inhibition of glycine oxidation that is observed in numerous inborn errors involving branched-chain amino acid metabolism is the result of reduction of the H-protein moiety of glycine synthase by electron derived from the oxidation of branched-chain alpha keto acids. Currently several approaches are being used to provide evidence relating to this hypothesis. The kinetic properties of this unique inhibitory mechanism are being studied to help us rule out the possiblity that the inhibition by branched-chain alpha keto acids is due to an allosteric binding of these compounds to glycine synthase. We are now attempting to identify a suitable cultured cell system that will enable us to investigate the effects of alterations in branched-chain amino acid concentrations on the glycine synthase activity. In addition, an inhibitor of isovaleryl CoA dehydrogenase, hypoglycin, is known and could be used to mimic an inborn error of metabolism known to result in abnormal glycine oxidation.